Inborn errors of Amino Acid and Carbohydrate Metabolism

Question 1

What is the definition of inborn errors of amino acid metabolism?

Answer 1

Inherited disorder involving enzyme for AA metabolism due to gene mutaiton.

Question 2

What is the aetiology and epidemiology of phenylketonuria?

Answer 2

AR inherited - classical PKU (complete deficiency of PHN HOXylase) OR hyperphenylalanemia (deficiency of PHN Hoxylase cofactor).

1/15k

Question 3

What is the aetiology and epidemiology of Homocysteinuria?

Answer 3

AR. Due to deficiency in cystathionine synthase.

1/344k

Question 4

What is the aetiology of occulocutaneous albinism?

Answer 4

Oculocutaneous albinism (OCA): Two distinct AR forms.

· OCAI: gene defect on Chr11, tyrosinase gene.

· OCAII: generalsied albinism due to gene on Chr15, lack of protein to transport tyrosine across membrane.

Related to chr abnormalities (i.e. PWS/Angelmann) with deletion on Chr15.

Question 5

What is the epidemiology of OCA?

Answer 5

OCAI: 1/40k, OCAII: 1/15k.

Question 6

What may you find in the history and exam in someone with PKU?

Answer 6

Infants have normal birth with progressive cognitive development, lost 4IQ/month, severe vomiting. Older children: hyperactive, purposeless movements, rhythmic rocking

if not picked up antenatal – blonder than siblings, musky odor, sebhorreic or eczemoid rash, hypertonic with hyperactive deep reflexes.

Question 7

What would you find in the history and exam of HCU?

Answer 7

normal birth. Infants have failure to thrive, developmental delay and epilepsy. >3yo have subluxation of the ocular lens leading to sever myopia. Astigmatism, glaucoma, retinal detachment, optic atrophy, nenurodevelopmental delay.

Skeletal abnormalities, long limbs, arachnodactily, pes cavus, genus valgum and high arched palate.

Question 8

What would you find in the history and exam of a child with OCA?

Answer 8

Lack of pigment at birth, low visual acuity, absent binocular vision, blindness and skin cancer. OCAII is milder.

lack of skin, eye, hair pigmentation, strabismus, red reflex, pink iris at birth.

Question 9

What investigations would you do for PKU?

Answer 9

high phenylalalnie levels 48h after birth, Guthrie test.

Question 10

What investigations would you do for HCU?

Answer 10

high methionone and homocysteine in plasma, osteoporosis on XR.

Question 11

What investigations would you do for OCA?

Answer 11

genetic analysis

Question 12

What is the management of PKU, HCU and OCA?

Answer 12

PKU: total avoidanc to maintain blood levels under 0.6nmol/l.

HCU: pyroxidine (100-500mcg/d) and folic acid. Avoid animal proteins, plant ok. Avoid OCP.

OCA: avoid sunlight, sun protection, regulat opthalmology checkup.

Question 13

What are the complications of PKU/ HCU and OCA?

Answer 13

PKU: CNS impairment and LD if phenylalanine levels high.

HCU: high homocysteine levels cause IHD and thromboembolic disease in adults.

OCA: nystagmus, strabism and skin cancer

Question 14

What is the prognosis of PKU, HCU and OCA?

Answer 14

PKU: Excellent if treatment within first 2-3wk of life. Outcome variable if delayed

HCU: good with tx

OCA: variable outcome.

Question 15

What is the definition of inborn errors of carbohydrate metabolism?

Answer 15

Glycogen storage disorders and galactosaemia occurring dnue to mutations in carbohydrate metabolism enzymes

Question 16

What is the aetiology of inborn error of carbohydrate metabolism?

Answer 16

GSD: enzymes for synthesis and degradaiton of glycogen. Abnormal quantity of glycogen produced.

Galactosaemia: disorder of galactose metabolism with high plasma levels

Question 17

What is the epidemiology of inborn errors of carbohydrate metabolism?

Answer 17

GSD 1/20k (Most G6PD), Galactosaemia 1/30k.

Question 18

What is the history and examination that you would find in a patient with an inborn error of carbohydrate metabolism?

Answer 18

GSD can vary harmless to lethal depending on subtype.

· Von Giercke, G6PD (Ia) – short stature, hepatomegaly, round face, retardation, platelet dysfunction, hypoglycaemia and lactic acidosis.

· Pompe disease (II) – Muscle weakness and cardiomyopathy.

Galactosaemia: Neonatal jaundice (initially unconj, then conj), hepatosplenomegaly, vomiting, hypoglycaemia and seizures. Later stunt growth and development.

Question 19

What investigations would you do for inborn errors of carbohydrate metabolism?

Answer 19

Definitive diagnosis requires proof of lack of enzyme.

GSD have low glucose, high uric acid, lactate and TGs. Liver biopsy is diagnostic.

Galactosaemia screened for in the UK.

Question 20

What is the management of inborn errors of carbohydrate metabolism?

Answer 20

GSD: slow infusion of glucose to maintain levels until lower doses of carbohydrates that are longer acting can be re introduced into the diet.

Galactosaemia: complete elimination of galactose form diet. Breastfeeding is a no

Question 21

What are the complications of GSD and galactosaemia?

Answer 21

GSD: Hepatic adenomas and HCCs, renal damage from hyperuricaemia, HTN, bleeding tendency leading to low Fe.

Galactosaeima: short stature, infertility, learning difficulties.

Question 22

What is the prognosis of GSD and galactosaemia?

Answer 22

GSD: most complications in adults where there was poor childhood control

Galactosaemia: if untreated, rapidly fatal