Biochemical Genetics

PKU

Gene: PAH- Phenylalanine Hydroxylase

Galactosemia

Gene: GALT- GALT enzyme

Gaucher

Gene: GBA gene- Beta glucocerebrosidase

Tay Sachs

Gene: HEXA- Beta Hexosaminidase A

Alkaptonuria

Gene: HDG- homogentisate 1,2-dioxidase

MPS1

Gene: IUDA- alpha-L-iduronidase

Hyperphenylalaninemia Secondary to Tetrabiopterin (BH4) deficiency

Genes: CCHI, PCHDI, PT5, QDPR

Biotinidase

Gene: BTD

Cystinuria

Gene: SLC3a or SLC7A9

Primary Carnitine Deficiency

Gene: SLC22A5

Familial Hypercholesterolemia

Gene: LDLR

Toxic Substrate

PKU, Tay Sachs, Gaucher, Galactosemia

Substrate Interferes with Function

Alkaptonuria, MPS1

Accumulation of Minor Metabolite

PKU, Urea Cycle Defects

Cofactor/Coenzyme Defect

BH4 deficiency

Transport Defects

Cystinuria, Primary Carnitine Deficiency

Recycling Defects

Biotinidase

Receptor Defects

Familial Hypercholesterolemia

PKU Labs

Increased Phe, low Tyr; abnormal Phe:Tyr

Galactosemia Labs

decreased GALT enzyme activity, high Gal-1-P levels

Gaucher Labs

decreased beta-glucocerebrosidase activity, accumulation of GL1

Tay Sachs Labs

decreased HEXA enzyme activity

Urea Cycle Labs

hyperammonemia, plasma aas, orotic acid levels

OTC- increased glutamine, increased orotic acid

BH4 deficiency Labs

increased Phe, low/normal Tyr

Biotinidase Lab

FAH Labs

hypercholesterolemia

Primary Carnitine Deficiency Labs

Low/absent CO on acylcarnitine levels, increased CK, low free carnitine

PKU Symptoms

ID, seizures, movement disorders, musty odors, decreased skin/hair pigmentation

Galactosemia Symptoms

feeding problems, liver failure, bleeding, FTT, neonatal death

Gaucher Symptoms

hepatosplenomegaly, cytopenias, growth retardation, bone disease, lung disease

Tay Sachs Symptoms

normal at birth/early development, progressive muscle weakness, cherry red spot in retina, exaggerated startle response

Alkaptonuria Symptoms

dark urine, ochronosis, aortic/mitral valve calcification, arthritis of spine, kidney stones, prostate stones

MPS 1 Symptoms

hepatosplenomegaly, corneal clouding, cardiac, skeletal, hearing loss

Urea Cycle Symptoms

FTT, anorexia, extreme lethargy, altered mental states, death

BH4 deficiency symptoms

muscle tone, rigidity, DD, tremors, seizures, ID

Biotinidase Symptoms

DD, hypotonia, seizures, ataxia, vision loss, alopecia, rash, candidiasis 

Cystinuria Symptoms

kidney/bladder stones, UTIs, renal insufficiency, hematuria

FAH Symptoms

HIGH cholesterol, atherosclerosis, premature coronary artery disease and heart disease, xanthomas

Primary Carnitine Deficiency Symptoms

metabolic decompensation often triggered by fasting, myopathy of heart/skeletal muscle

Homocystinuria

Gene: CBS- cysteine-B synthase

Homocystinuria Labs

increased homocysteine levels and increased methionine

Homocystinuria Symptoms

Marfanoid features, DD, seizures, psychotic symptoms