Neonatal Emergencies:The Missed Ones

Dr. Manoj Ghoda Consultant Gastroenterologist

mkghoda@yahoo.com, +91 9824024165

Greetings from Ahmedabad

Next capital of India

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NBS and beyond….

ICMR puts estimates of prevalence at 1:1400 to 1:2100

Certain inbreeding communities, small communities and small isolates may have disproportionately high incidence and prevalence of IEM

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Metabolic Emergencies

Why do we miss metabolic emergencies ? What historical and clinical features should alert us

about the underlying metabolic cause? What tests are useful once a metabolic disease is

suspected? What are the common metabolic emergencies in

routine practice?

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Why are Metabolic emergencies Missed?

Symptoms are non-specific and could be easily confused with routine pediatric problems – Vomiting for gastritis/gastroenteritis.– Altered sensorium to meningitis/viral encephalitis– Altered respiration for respiratory infections or

asthma.– Jaundice for hepatitis.

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Why are Metabolic emergencies Missed? Some routine illnesses themselves precipitate

metabolic emergencies

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Why are Metabolic emergencies Missed? Tests are not easily available

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Why are Metabolic emergencies Missed? We don’t think about it! Or we think what we want

to think !!

Only srmat poelpe can raed tihs. I cdnuolt blveiee taht I cluod aulaclty uesdnatnrd waht I was rdanieg. The phaonmneal pweor of the hmuan mnid, aoccdrnig to a rscheearch at Cmabrigde Uinervtisy, it deosn't mttaer in waht oredr the ltteers in a wrod are, the olny iprmoatnt tihng is taht the frist and lsat ltteer be in the rghit pclae. The rset can be a taotl mses and you can sitll raed it wouthit a porbelm. Tihs is bcuseae the…….

Why are Metabolic emergencies Missed? Only srmat poelpe can raed tihs. I cdnuolt blveiee taht I cluod

aulaclty uesdnatnrd waht I was rdanieg. The phaonmneal pweor of the hmuan mnid, aoccdrnig to a rscheearch at Cmabrigde Uinervtisy, it deosn't mttaer in waht oredr the ltteers in a wrod are, the olny iprmoatnt tihng is taht the frist and lsat ltteer be in the rghit pclae. The rset can be a taotl mses and you can sitll raed it wouthit a porbelm. Tihs is bcuseae the…….

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When Should the Alarm Bell Ring?

In your practice, if you see a child with …

Acute illness following a period of normalcy Intermittent illness for no obvious reason Recurrent unexplained vomiting Failure to thrive Aversion to certain food or the illness starting with

particular food

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When to Suspect an IEM?

Or a child with …

Rapid deterioration for no obvious reasons Rapidly progressive encephalopathy of obscure

origin Lethargy and coma Hypotonia, seizures, especially if hard to control Intractable hiccups

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When to Suspect an IEM?

Or if the child has ...

Apnea or respiratory distress Sepsis, particularly with E. Coli Unusual odor Jaundice Dysmorphic features Organomegaly

Believe me

It is not difficult….

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Case Study

A Child with Recurrent Attacks of Asthma

History

A 16 month old boy was referred for “recurrent attacks of asthma”

He was born out of a 2nd degree consanguineous marriage and was the first child of the parents

FTND and birth weight was 2.7 Kg Pregnancy was uneventful There was no notable family history or past medical

history

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Observations Soon after birth the child had recurrent episodes of

“asthma” – Each time he would be given a cocktail of nebulizers and

antibiotics with oxygen and the rest and would recover enough to be discharged, only to be admitted again

On an average, he had one admission every fortnight He had vomiting and failure to thrive Xrays and blood tests were unremarkable, he had no

evidence of pneumonia on xrays He was referred with a suspicion of metabolic cause

underlying his illness

Observations (Contd.) The child appeared small for his age and his weight was in the

5th centile for his age. He had tachypnea; Chest was clear on clinical examination CNS revealed Hypotonia but otherwise unremarkable Normal CXR Normal CBC, LFT, PT, Blood Sugar and Creatinine Blood Urea 12 mg. High Ammonia 188 mmmol (++) Normal Lactate Metabolic screening by urine was normal Blood Gases on room air showed

– pH 7.48– pO2 112, pCO2 28, HCO3 17

Recapping …

We have a hyperventilating patient– He is born out of a consanguineous marriage– He has unexplained vomiting, failure to thrive and

hypotonia– He has normal chest on clinical examination and normal

chest x-ray– Normal sugar, normal anion gap– Low urea and high ammonia with normal liver functions,

normal PT, normal albumin; and normal lactate– Respiratory alkalosis

True or False?

If any problem is recurrent; it may be due to underlying metabolic disease

Respiratory distress could be a major manifestation of underlying metabolic disease

Unexplained vomiting and failure to thrive are two of the common manifestations of metabolic illness.

Consanguinity is more likely to produce metabolic disease

Asthma or any other respiratory illness usual to childhood would have caused respiratory acidosis and not respiratory alkalosis

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Some common metabolic disorders leading to emergency in Newborn

Galactosemia, Tyrosinemia Organic Acidopathies Urea Cycle Disorders Maple Syrup Urine Disease Glycogen Storage Disorders Nonketotic Hyperglycinemia Cystic Fibrosis

Initial Screening Tests CBC

– Neutropenia is frequent in some Organic Acidemias– Megaloblastic Anemia in MMA– Adler–Reilly bodies in storage disorders. Glycogen granule in GSD

Electrolytes, ABG to evaluate for acidosis and anion gap Glucose, LFT and RFT Ammonia, Lactate, Pyruvate Galactosemia Screening tests Uric Acid

Initial Screening Tests (Contd.)

Urinalysis – Urinary pH– Reducing substances– Ketones

The presence of ketones is unusual even in sick neonates and suggests an Organic Acidemia. High false positive rate

– Absent ketones in hypoglycemia may suggest Fatty Acid Disorders

DNPH test for MSUD

Other Screening Tests

Urine organic acids by GC/MS while the patient is ill Plasma amino acids MS/MS, while the patient is ill Total Carnitine, Free Carnitine and Acylcarnitine

profile

Back to our Case

Analysis based on clinical features and basic investigations

Respiratory Alkalosis Psychogenic Hyperventilation Hypoxia Hyperammonemia Excessive Mechanical Ventilation CNS Causes

– Stroke, Subarachnoid Hemorrhage, Meningitis Drugs

– Doxapram, Aspirin, Caffeine and Coffee Abuse Fever, which stimulates the respiratory centre in the

brainstem Pregnancy

Respiratory Alkalosis (Contd.)

Hyperventilation secondary to cerebral edema is a common early finding in hyperammonemic attacks that results in respiratory alkalosis.

Hypoventilation and respiratory arrest follow as pressure increases on the brain stem

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Hyperammonemia Liver Disorders Urea Cycle Disorders Organic Acidemia Fatty Acid Oxidation Disorders Energy Metabolism Disorders

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Could this Patient have Urea Cycle Disorder?

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Urea Cycle Disorders

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Lab Diagnosis Plasma Ammonia Plasma Amino Acids

– Low/Absent Citrulline Proximal Defects – OTC/CPS1/NAGS

– High Citrulline Distal Defects

– Argininosuccinate - ASL– High Arginine – ARG – High Ornithine – ORNT1– High GLN, ASN, ALA

All UCDs – Ammonia Sump Urinary Orotate

– High in all UCDs except CPS1 and NAGS therefore used to differentiate these from OTC

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Tandem Mass Spectrometry (MS/MS)

High Citrulline High Arginosuccinic Acid Low Arginine

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Severe Illness Usually normal the first 24 hours Symptoms of Hyperammonemia within 1-3 days

include: – Feeding intolerance– Vomiting– Lethargy– Irritability– Respiratory Distress (Hyperventilation)– Seizures– Coma

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Mild Disease Mild/Partial Defects/Female Carriers of OTC

– hyperammonaemia triggered by illness or stress First episode can occur all the way into adulthood LOA, cyclical vomiting, lethargy, psychosis Encephalopathic (slow-wave) EEG pattern Brain atrophy on MRI after repeated episodes

So... My humble request is...

Think metabolic.....

When all is not well

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Thank you

Dr Manoj K Ghoda MD, MRCPConsultant Gastroenterologist Special interest in Neonatal and Pediatric Liver and Metabolic Diseasesmkghoda@yahoo.com+91 9824024165