MPS & Other
Rare Genetic Diseases
Rare Genetic Diseases
Mucopolysaccharidoses, commonly referred to as MPS, are a group of rare genetic metabolic disorders, and are regarded as lysosomal storage disorders.
Normally, the body makes enzymes to break down materials for our cells. For people with MPS and related diseases, the missing or insufficient enzyme prevents that normal process for the sugar glycosaminoglycans (or mucopolysaccharides), so they become stored in almost every cell of the body. As a result, cells do not function properly and cause progressive damage to the person throughout the body, including the heart, bones, joints, respiratory system, and nervous system. While the disease is not immediately apparent at birth, signs and symptoms develop with age as more cells become damaged by the accumulation of cell deposits. Most patients usually do not live through their twenties.
Mucopolysaccharidoses exist in a total of seven types — MPS I, II, III, IV, VI, VII, IX — and numerous subtypes. There are no type V and VIII. The seven types are subdivided to subtypes according to enzyme defect and symptoms shown by the body. Although each type of MPS is clinically different, most patients generally experience a period of normal development and then followed by a decline in physical and/or mental function.
Number of MPS patients in our organisation = 25; Number of patients with rare diseases in our organisation = 36; Total Number of MPS + Rare Diseases Patients = 61 (Updated: 11 April 2024)
Hurler
Syndrome
Syndrome
MPS 1-H
Incidence Estimates
About 1 per 100,000 births
Cause
Lack of the enzyme alpha-L-iduronidase
Both parents also carry the defective gene
Symptoms and Treatments
MPS I therapy approval dates: Aldurazyme (laronidase) – Hong Kong: Mar 2008; FDA: 30 Apr 2003; EMEA: Jun 2003
Hurler-Scheie
Syndrome
Syndrome
MPS 1-HS
Incidence Estimates
About 1 per 115,000 births
Cause
Lack of the enzyme alpha-L-iduronidase
Both parents also carry the defective gene
Symptoms and Treatments
MPS I therapy approval dates: Aldurazyme (laronidase) – Hong Kong: Mar 2008; FDA: 30 Apr 2003; EMEA: Jun 2003
Scheie
Syndrome
Syndrome
MPS 1-S
Our MPS1 members
2
Incidence Estimates
About 1 per 500,000 births
Cause
Lack of the enzyme alpha-L-iduronidase
Both parents also carry the defective gene
Symptoms and Treatments
MPS I therapy approval dates: Aldurazyme (laronidase) – Hong Kong: Mar 2008; FDA: 30 Apr 2003; EMEA: Jun 2003
Hunter
Syndrome
Syndrome
MPS II A
Incidence Estimates
About 1 per 100,000 to 150,000 male births
Cause
Lack of the enzyme iduronate sulfatase
The defective gene was passed from the mother
Symptoms and Treatments
Similar to Hurler syndrome but much milder
MPS II therapy approval dates: Elaprase (idursulfase) – Hong Kong: Oct 2008; FDA: Jul 2006; EMEA: Jan 2007
Hunter
Syndrome
Syndrome
MPS II B
Our MPS 2 Members
3
Incidence Estimates
About 1 per 100,000 to 150,000 male births
Cause
Lack of the enzyme iduronate sulfatase
The defective gene was passed from the mother
Symptoms and Treatments
Similar to Hurler syndrome but much milder
MPS II therapy approval dates: Elaprase (idursulfase) – Hong Kong: Oct 2008; FDA: Jul 2006; EMEA: Jan 2007
Sanfilippo
Syndrome
Syndrome
Our Members
9
Incidence Estimates
About 1 per 24,000 to 70,000 births
Cause
Lack of the enzyme heparan sulphate
Morquio
Syndrome
Syndrome
Our Members
8
Incidence Estimates
About 1 per 200,000 births
Cause
Lack of the enzyme keratan sulphate
Both parents also carry the defective gene
Symptoms and Treatments
MPS IV therapy approval dates: Naglazyme (Galsulfase) – FDA: May 2005; Europe: Jan 2006
Maroteaux-Lamy
Syndrome
Syndrome
Our Members
3
Incidence Estimates
About 1 per 215,000 births
Cause
Lack of the enzyme dermantan
Both parents also carry the defective gene
Symptoms and Treatments
In May 2005, Naglazyme received marketing approval from the U.S. Food and drug Administration for the treatment of MPS VI patients. Shortly thereafter, in January 2006, Naglazyme received marketing authorization in the European Union.
Sly
Syndrome
Our Members
0
Incidence Estimates
Natowicz Syndrome
Our Members
0
Incidence Estimates
Only 1 reported case in the world
Cause
Lack of the enzyme hyaluronidase
Mucolipidosis
Our Members
0
Incidence Estimates
About 2-3 per 100,000 births
Cause
Lack of enzymes to break down carbohydrates and lipids
Symptoms and Treatments
Early onset may include rigid arms and shoulders, later on with carpal tunnel syndrome. Half of the patients have hearing impairment and a mild form of mental impairment.
Fabry disease
Our Members
8
Cause
Lack of the enzyme alpha-galactosidase A
Symptoms and Treatments
Pain or strange feeling, sometimes even burning feeling, at the hands and feet during childhood or adolescence.
Dark purple skin colour at the lower abdomen, thigh, prostate or external sexual organ.
FDA approval date: Fabrazyme – 3 Aug 2001
Gaucher's disease
Our Members
1
Incidence Estimates
About 1 per 100,000 births
Cause
Deficiency of enzyme glucocerebrosidase (also known as acid β-glucosidase)
Symptoms and Treatments
Hepatosplenomegaly, sports regulatory function of the imbalance, small limbs, bone deformation, fracture easily.
FDA approval date: Cerezyme – 23 May 1994
Pompe disease
aka
Glycogen storage disease Type II
Our Members
5
Incidence Estimates
About 1 per 400,000 births
Cause
Lack of acid maltase
Symptoms and Treatments
Ventricular fat or less rapid expansion of the heart, eventually causing obstruction to aortic flow, muscle weakness.
Death by around 2 years old
FDA approval date: Myozyme – 28 Apr 2006
Atypical
Hemolytic Uremic Syndrome
Hemolytic Uremic Syndrome
Our Members
2
Incidence Estimates
Estimated: About 1 per 500,000 births (USA)
Symptoms and Treatments
Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, life-threatening, progressive disease that frequently has a genetic component. In most cases it is caused by chronic, uncontrolled activation of the complement system, a branch of the body’s immune system that destroys and removes foreign particles. The disease affects both children and adults and is characterized by systemic thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to stroke, heart attack, kidney failure, and death.
Multiple sclerosis
Our Members
1
Incidence Estimates
About 2-5 per 100,000 births
Cause
Virus or inflammation affecting the immune system
Symptoms and Treatments
Neurological symptoms such as visual disorders, tremor, numbness, dizziness, weakness, leg stiffness. These may go away or sustain, or worsen over time.
More common in women
Phenylketouria (PKU)
Our Members
1
Incidence Estimates
Varies greatly in regions and ethnicity
Cause
Lack of an enzyme to breakdown amino acids
Symptoms and Treatments
Infants abnormally drowsy, unusually light skin. Feeding difficulties. Severe mental retardation if no treatment.
Sotos Syndrome
aka
Cerebral Gigantism
Our Members
0
Incidence Estimates
About 1 per 14,000 births
Cause
Mutation in a gene
Symptoms and Treatments
Excessive growth before and after birth, abnormally prominent forehead, and developmental delays in most children.
Hereditary
epidermolysis bullosa
epidermolysis bullosa
Our Members
1
Incidence Estimates
About 1 per 50,000 births
Cause
Mutation in the keratin gene
Symptoms and Treatments
Recurring painful blisters and open sores, often after minor trauma, due to unusually fragile nature of the skin.
Urea cycle disorder
Our Members
1
Incidence Estimates
About 1 per 100,000 births
Cause
Lack of an enzyme in the urea cycle to remove ammonia from the blood stream
Symptoms and Treatments
Amine caused by high blood coma, vomiting.
Glycogen storage disease
Our Members
1
Incidence Estimates
About 1 per 100,000 births
Cause
Lack of enzymes to breakdown glycogen
Symptoms and Treatments
Drowsiness, trembling, slow growth, increased abdominal circumference, fat accumulation in the cheek into a rounded doll-like. Nosebleeds or ears to inflammation, gingivitis, sores symptoms. After the emergence of rickets, anemia symptoms. Gland tumor complications such as liver, progressive renal failure, kidney stones, gout, anemia, osteoporosis, etc.
Interstitial
deletion of chromosome 3q23 to 3q25
deletion of chromosome 3q23 to 3q25
Our Members
1
Glutaric aciduria Type I
Our Members
1
Cause
Lack of an enzyme
Symptoms and Treatments
Neurological symptoms such as muscle stiffness, hand-foot-progressive chorea, paralysis, corner arch anti-sheets, legs turned out, the body was arcuate and so on, may have epilepsy, or sleeping with acute onset of coma.
Williams Syndrome
Our Members
1
Incidence Estimates
About 1 per 20,000 births
Cause
Williams syndrome, also known as Williams–Beuren syndrome, is a rare neurodevelopmental disorder characterized by: a distinctive, “elfin” facial appearance, along with a low nasal bridge; an unusually cheerful demeanor and ease with strangers; developmental delay coupled with strong language skills; and cardiovascular problems, such as supravalvular aortic stenosis and transient high blood calcium.
Symptoms and Treatments
Huntington's Disease
Our Members
1
Incidence Estimates
Affects 1 out of 1,000,000 in people of Asian descent
Cause
Huntington’s Disease is a rare inherited brain disorder caused by a mutation of a specific gene on chromosome 4.
Symptoms and Treatments
Since the most obvious symptoms of Huntington’s Disease are abnormal involuntary body movements, it is often simply referred to as chorea.
Huntington’s Disease, however, is not as simple as it seems. Chorea which typically causes an unsteady gait is only one of the first symptoms of the disease. Other accompanying symptoms include swallowing and speech difficulties. As the disease progresses, it also affects a number of mental and cognitive abilities, as well as certain aspects of personality.
Huntington’s Disease patients usually develop symptoms after mid-adult life. In the later stage of the disease, eating, speech and mobility are extremely difficult if not impossible, and they may eventually become bedridden, facing an increased risk of infection.
Each child of a person with Huntington’s Disease has a 50% chance of inheriting the gene. It is devastating not only to the patients but also to their families.
There is, at present, no cure for Huntington’s Disease, but treatments are available to slow down the symptoms and help the patients function for as long and as comfortably as possible. The care and support of family and friends is profoundly critical to Huntington’s Disease patients.
Huntington’s Disease, however, is not as simple as it seems. Chorea which typically causes an unsteady gait is only one of the first symptoms of the disease. Other accompanying symptoms include swallowing and speech difficulties. As the disease progresses, it also affects a number of mental and cognitive abilities, as well as certain aspects of personality.
Huntington’s Disease patients usually develop symptoms after mid-adult life. In the later stage of the disease, eating, speech and mobility are extremely difficult if not impossible, and they may eventually become bedridden, facing an increased risk of infection.
Each child of a person with Huntington’s Disease has a 50% chance of inheriting the gene. It is devastating not only to the patients but also to their families.
There is, at present, no cure for Huntington’s Disease, but treatments are available to slow down the symptoms and help the patients function for as long and as comfortably as possible. The care and support of family and friends is profoundly critical to Huntington’s Disease patients.
WAGR Syndrome
Our Members
1
Incidence Estimates
Aniridia: 1/40,000 ~1:100,000
Cause
WAGR syndrome is a rare genetic syndrome in which affected children are predisposed to develop Wilms tumour (a tumour of the kidneys), Aniridia (absence of the coloured part of the eye, the iris), Genitourinary anomalies, and Retardation. The G is sometimes instead given as “gonadoblastoma,” since the genitourinary anomalies are tumours of the gonads (testes or ovaries).
Prader-Willi Syndrome
Our Members
2
Incidence Estimates
1:12,000-15,000
Cause
Prader–Willi syndrome is a rare genetic disorder in which 7 genes (or some subset thereof) on chromosome 15 (q 11–13) are deleted or unexpressed (chromosome 15q partial deletion) on the paternal chromosome. Characteristic of PWS is “low muscle tone, short stature, incomplete sexual development, cognitive disabilities, problem behaviors, and a chronic feeling of hunger that can lead to excessive eating and life-threatening obesity.
Kabuki Syndrome
Our Members
0
Incidence Estimates
1/32,000 (Japan)
Kabuki syndrome is a rare genetic syndrome. Current statistics indicate somewhere between 1 and 10,000 and 1 in 32,000 people have Kabuki syndrome. “Genetic” means the individual is born with a condition and the cause of that condition resides in his or her genetic makeup. Genetic disorders can be passed down from one generation to the next (like Muscular Dystrophy) or could be a spontaneous genetic mutation caused by an error in DNAi replication. Genetic disorders like Down syndrome can occur with abnormalities at the chromosomal level, whereas other syndromes, like Kabuki syndrome, reside at the specific gene level.
Reference: Click here for details
Osteogenesis Imperfecta
Our Members
1
Incidence Estimates
About 1 per 20,000 live births (USA)
Symptoms and Treatments
People with Osteogenesis Imperfecta are born with defective connective tissue, or without the ability to make it, usually because of a deficiency of type I collagen.
8 types of OI can be distinguished. Most cases are caused by mutations in the COL1A1 and COL1A2 genes.
Leigh Disease
Our Members
0
Incidence Estimates
At least 1 in 40,000 newborns
Symptoms and Treatments
Leigh syndrome is a severe neurological disorder that typically arises in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within a couple of years, usually due to respiratory failure. A small number of individuals develop symptoms in adulthood or have symptoms that worsen more slowly.
Reference: Click here for details
Spinocerebellar Atrophy Type 35 and Spondyloepiphyseal Dysplasia
Our Members
1
Leber's
hereditary
optic
neuropathy
hereditary
optic
neuropathy
Our Members
1
Cause
Usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations are at nucleotide positions 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria.
Symptoms and Treatments
A mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males. LHON is only transmitted through the mother, as it is primarily due to mutations in the mitochondrial (not nuclear) genome, and only the egg contributes mitochondria to the embryo. Men cannot pass on the disease to their offspring.
Congenital Central
Hypoventilation Syndrome (CCHS)
Hypoventilation Syndrome (CCHS)
Our Members
1
Incidence Estimates
1 in 200,000 newborns
Cause
The underlying cause of CCHS is mutation in the PHOX2B gene.
Symptoms and Treatments
Congenital central hypoventilation syndrome (CCHS) is a rare lifelong and life-threatening disorder. CCHS affects the central and autonomic nervous system which controls many of the automatic functions in the body such as heart rate, blood pressure, sensing of oxygen and carbon dioxide levels in the blood, temperature, bowel and bladder control, and more. The most recognized symptom of CCHS is the inability to control breathing that varies in severity, resulting in the need for life-long ventilatory support during sleep in some patients or all the time in others. There are estimated to be 1000 – 1200 cases of CCHS world-wide. CCHS affects males and females equally. Currently, there is no cure for CCHS.
Multiple
Epiphyseal Dysplasia
Epiphyseal Dysplasia
Our Members
1
Incidence Estimates
The incidence of dominant multiple epiphyseal dysplasia is estimated to be at least 1 in 10,000 newborns. The incidence of recessive multiple epiphyseal dysplasia is unknown. Both forms of this disorder may actually be more common because some people with mild symptoms are never diagnosed.
Cause
Multiple epiphyseal dysplasia is a disorder of cartilage and bone development primarily affecting the ends of the long bones in the arms and legs (epiphyses). The majority of individuals are diagnosed during childhood; however, some mild cases may not be diagnosed until adulthood.
Symptoms and Treatments
There are two types of multiple epiphyseal dysplasia, which can be distinguished by their pattern of inheritance. Both the dominant and recessive types have relatively mild signs and symptoms, including joint pain that most commonly affects the hips and knees, early-onset arthritis, and a waddling walk. Although some people with multiple epiphyseal dysplasia have mild short stature as adults, most are of normal height.
Recessive multiple epiphyseal dysplasia is distinguished from the dominant type by malformations of the hands, feet, and knees and abnormal curvature of the spine (scoliosis). About 50 percent of individuals with recessive multiple epiphyseal dysplasia are born with at least one abnormal feature, including an inward- and upward-turning foot (clubfoot), an opening in the roof of the mouth (cleft palate), an unusual curving of the fingers or toes (clinodactyly), or ear swelling. An abnormality of the kneecap called a double-layered patella is also relatively common.
Duchenne
Muscular Dystrophy
Muscular Dystrophy
Our Members
1
Incidence Estimates
1 in 5,000 males, rare in females
Cause
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness. It is one of nine types of muscular dystrophy. DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact.
Symptoms and Treatments
Symptom onset is in early childhood, usually between ages 3 and 5. The disease primarily affects boys, but in rare cases it can affect girls.
Muscle weakness can begin as early as age 3, first affecting the muscles of the hips, pelvic area, thighs and shoulders, and later the skeletal (voluntary) muscles in the arms, legs and trunk. The calves often are enlarged. By the early teens, the heart and respiratory muscles also are affected.
Survival into the early 30s is becoming more common, and there are cases of men living into their 40s and 50s.
CTNNB1 Syndrome
Our Members
1