Autosomal Recessive Diseases of Childhood

Phenylketonuria (Autosomal Recessive)
Prevalence: 1 in 10,000 Caucasians
Def. enzyme: phenylalanine hydroxylase, or lack of its cofactor, tetrahydrobiopterin.
Build-up: Phenylalanine
Symptoms: Phenylpyruvate in urine (metabolized from phenylalanine), severe mental retardation, often light colored hair and skin
Rx: Kuvan (sapropterin), low protein diet, Most US facilities recommend that phenylalanine levels be maintained in the range of 2-6 mg/dL (120-360 µmol/L).

Alkaptonuria (Autosomal Recessive)
Prevalence: 1 in 100,000
Def. enzyme: homogentisate 1,2 dioxygenase
Build-up: Phenylalanine and Tyrosine which leads to toxic build-up of homogentisate.
Symptoms: Dark urine from protein build-up when left to stand, NOT immediately; "black bones", osteoporosis, increased pigmentation in cartilage of ear, valvular heart and aortic disease, hearing loss after age 40.
Rx: In the past Hi Dose Vit C and protein restriction, but recent studies have shown not effective. Possible new treatment is nitisinone, but this will cause tyrosine build-up, effects unknown.

Maple Syrup Urine Disease (Autosomal Recessive)
Prevalence: 1 in 200,000
Def. enzyme: alpha-ketoacid dehydrogenase
Build-up: Isoleucine, Leucine, Valine (Mnemonic: I Like Vermont Maple Syrup)
Symptoms: Ketoacidosis, Neuro symptoms, Sweet smelling, normal-looking urine
Rx: Restrict Branch chain AA consumption

Hyperprolinemia (Autosomal Recessive)
Prevalence: 1 in 200,000 in the US
Def. enzyme: proline oxidase
Build-up: proline in blood, urine, CSF
Symptoms: seizures, intellectual dysfunction, schizophrenia
Rx: None

Homocystinuria (Autosomal Recessive)
Prevalence: 1 in 300,000
Def. enzyme: Cystathionine Beta Synthase (see diagram)
Build-up: Homocysteine
Symptoms: Lens dislocation leading to near-sight, high stroke risk, thromboembolic risk, osteoporosis, learning disability, pectus carinatum/excavatum
Rx: High dose Vit. B6, Betaine (Cystadene) to clear Homocysteine, low protein (low methionine) diet.